Melatonin-induced augmentation of collagen deposition in cultures of fibroblasts and myofibroblasts is blocked by luzindole – a melatonin membrane receptors inhibitor

Drobnik, Jacek; Owczarek, Katarzyna; Piera, Lucyna; Tosik, Dariusz; Olczak, Sławomir; Ciosek, Joanna; Hrabec, Elżbieta

doi:10.1016/s1734-1140(13)71041-7

Cited by 28 publications

(21 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We and others have previously demonstrated that melatonin's cardioprotective effect was partially mediated by its membrane receptors. Luzindole, a specific melatonin membrane receptor antagonist, inhibited its protective actions [10,13,59]. In this study, both in vivo and in vitro data demonstrated that activation of Notch1/ Hes1 signaling by melatonin treatment was abolished by luzindole administration.…”

Section: Discussionsupporting

confidence: 51%

Membrane receptor‐dependent Notch1/Hes1 activation by melatonin protects against myocardial ischemia–reperfusion injury: in vivo and in vitro studies

Liu

Lü

et al. 2015

Journal of Pineal Research

View full text Add to dashboard Cite

Melatonin confers profound protective effect against myocardial ischemia-reperfusion injury (MI/RI). Activation of Notch1/Hairy and enhancer of split 1 (Hes1) signaling also ameliorates MI/RI. We hypothesize that melatonin attenuates MI/RI-induced oxidative damage by activating Notch1/Hes1 signaling pathway with phosphatase and tensin homolog deleted on chromosome 10 (Pten)/Akt acting as the downstream signaling pathway in a melatonin membrane receptor-dependent manner. Male Sprague Dawley rats were treated with melatonin (10 mg/kg/day) for 4 wk and then subjected to MI/R surgery. Melatonin significantly improved cardiac function and decreased myocardial apoptosis and oxidative damage. Furthermore, in cultured H9C2 cardiomyocytes, melatonin (100 μmol/L) attenuated simulated ischemia-reperfusion (SIR)-induced myocardial apoptosis and oxidative damage. Both in vivo and in vitro study demonstrated that melatonin treatment increased Notch1, Notch1 intracellular domain (NICD), Hes1, Bcl-2 expressions, and p-Akt/Akt ratio and decreased Pten, Bax, and caspase-3 expressions. However, these protective effects conferred by melatonin were blocked by DAPT (the specific inhibitor of Notch1 signaling), luzindole (the antagonist of melatonin membrane receptors), Notch1 siRNA, or Hes1 siRNA administration. In summary, our study demonstrates that melatonin treatment protects against MI/RI by modulating Notch1/Hes1 signaling in a receptor-dependent manner and Pten/Akt signaling pathways are key downstream mediators.

show abstract

Section: Discussionsupporting

confidence: 51%

Membrane receptor‐dependent Notch1/Hes1 activation by melatonin protects against myocardial ischemia–reperfusion injury: in vivo and in vitro studies

Liu

Lü

et al. 2015

Journal of Pineal Research

View full text Add to dashboard Cite

show abstract

“…In this respect, it has been recently reported that melatonin induced augmentation of collagen deposition in fibroblasts and myofibroblasts through an effect that is prevented by luzindole, the blocker of MT 1 and MT 2 melatonin membrane receptors. 49 …”

Section: Discussionmentioning

confidence: 99%

Melatonin limits the expression of profibrogenic genes and ameliorates the progression of hepatic fibrosis in mice

Crespo

San‐Miguel

Fernández

et al. 2015

Translational Research

View full text Add to dashboard Cite

We investigated whether melatonin ameliorates fibrosis and limits the expression of fibrogenic genes in mice treated with carbon tetrachloride (CCl 4 ). Mice in treatment groups received CCl 4 5 mL/g body weight intraperitoneally twice a week for 4 or 6 weeks. Melatonin was given at 5 or 10 mg/kg/d intraperitoneally, beginning 2 weeks after the start of CCl 4 administration. Treatment with CCl 4 resulted in fibrosis evidenced by the staining of Van Gieson and a-smooth muscle actin (a-SMA) positive cells in the liver. At both 4 and 6 weeks, CCl 4 induced an increase in the messenger RNA levels of collagens I and III, transforming growth factor (TGF)-b, platelet-derived growth factor (PDGF), connective tissue growth factor (CTGF), amphiregulin, matrix metalloproteinase (MMP)-9, and tissue inhibitor of metalloproteinase (TIMP)-1. Protein concentrations of CTGF, amphiregulin, MMP-9, TIMP-1, and phospho-Smad3 were also significantly augmented in fibrotic mice. Melatonin successfully attenuated liver injury, as shown by histopathology and decreased levels of serum transaminases. Immunohistochemical staining of a-SMA indicated an abrogation of hepatic stellate cell activation by the indol. Furthermore, melatonin treatment resulted in significant inhibition of the expression of collagens I and III, TGF-b, PDGF, CTGF, amphiregulin, and phospho-Smad3. The MMP-9 activity decreased and the expression of nuclear factor erythroid-2-related factor 2 (Nrf2) increased in mice receiving melatonin. Data obtained suggest that attenuation of multiple profibrogenic gene pathways contributes to the beneficial effects of melatonin in mice with CCl 4 -induced liver fibrosis. (Translational Research 2015;165:346-357) Abbreviations: a-SMA ¼ a-smooth muscle actin; CCl 4 ¼ carbon tetrachloride; CTGF ¼ connective tissue growth factor; HSC ¼ hepatic stellate cell; MMP-9 ¼ matrix metalloproteinase 9; Nrf2 ¼ nuclear factor erythroid 2-related factor 2; PDGF ¼ platelet-derived growth factor; TGF-b ¼ transforming growth factor b; TIMP-1 ¼ tissue inhibitor of metalloproteinase 1 H epatic fibrosis is a reversible wound-healing response to either acute or chronic cellular injury from a wide variety of etiologies, characterized by an excessive deposition of extracellular matrix (ECM) resulting in liver dysfunction and irreversible cirrhosis. During liver fibrogenesis, hepatic stellate cells (HSCs) undergo activation to a a-smooth muscle actin (SMA)-positive myofibroblastic phenotype and synthesize excess ECM components, particularly collagen. 1 Among the numerous From the

show abstract

“…Interestingly, the data obtained on fibroblasts and myofibroblasts in vitro are contradictory when compared to those obtained in vivo. Melatonin increases collagen and GAG accumulation by myofibroblasts isolated from superficial wound models, the infarcted heart scar and bone cells . This process is dependent on activation of the melatonin membrane receptors on scar myofibroblasts, which are inhibited by luzindole, a blocker of both MT1 and MT2 melatonin membrane receptors .…”

Section: Further Perspectivesmentioning

confidence: 99%

“…Melatonin increases collagen and GAG accumulation by myofibroblasts isolated from superficial wound models, the infarcted heart scar and bone cells . This process is dependent on activation of the melatonin membrane receptors on scar myofibroblasts, which are inhibited by luzindole, a blocker of both MT1 and MT2 melatonin membrane receptors . The fact that melatonin's ability to modulate fibroblast function varies between in vivo and in vitro studies, indicates that mechanisms association of melatonin should rely on in vivo experiments.…”

Section: Further Perspectivesmentioning

confidence: 99%

Melatonin: the dawning of a treatment for fibrosis?

Jiang

et al. 2016

Journal of Pineal Research

View full text Add to dashboard Cite

show abstract

Melatonin-induced augmentation of collagen deposition in cultures of fibroblasts and myofibroblasts is blocked by luzindole – a melatonin membrane receptors inhibitor

Cited by 28 publications

References 18 publications

Membrane receptor‐dependent Notch1/Hes1 activation by melatonin protects against myocardial ischemia–reperfusion injury: in vivo and in vitro studies

Membrane receptor‐dependent Notch1/Hes1 activation by melatonin protects against myocardial ischemia–reperfusion injury: in vivo and in vitro studies

Melatonin limits the expression of profibrogenic genes and ameliorates the progression of hepatic fibrosis in mice

Melatonin: the dawning of a treatment for fibrosis?

Contact Info

Product

Resources

About